Association of patient-level characteristics with long-term outcomes after Fontan palliation: Rationale, design, and baseline characteristics of the Pediatric Cardiac Care Consortium Fontan cohort study.

BACKGROUND: The Fontan operation is used to palliate single ventricle congenital heart defects (CHD) but poses significant morbidity and mortality risks. We present the design, planned analyses and rationale for a long-term Fontan cohort study aiming to examine the association of patient characteristics at the time of Fontan with post-Fontan morbidity and mortality. METHODS AND RESULTS: We used the Pediatric Cardiac Care Consortium (PCCC), a US-based, multicenter registry of pediatric cardiac surgeries to identify patients who underwent the Fontan procedure for single ventricle CHD between 1 and 21 years of age. The primary outcomes are in-hospital Fontan failure (death or takedown) and post-discharge mortality through 2022. A total of 1461 (males 62.1%) patients met eligibility criteria and were included in the analytical cohort. The median age at Fontan evaluation was 3.1 years (IQR: 2.4-4.3). While 95 patients experienced in-hospital Fontan failure (78 deaths and 17 Fontan takedown), 1366 (93.5%) survived to discharge with Fontan physiology and formed the long-term analysis cohort. Over a median follow-up of 21.2 years (IQR: 18.4-24.5) 184 post-discharge deaths occurred. Thirty-year post Fontan survival was 75.0% (95% CI: 72.3-77.8%) for all Fontan types with higher rates for current techniques such as lateral tunnel and extracardiac conduit 77.1% (95% CI: 73.5-80.8). CONCLUSION: The PCCC Fontan study aims to identify predictors for post-Fontan morbidity and mortality, enabling risk- stratification and informing surveillance practices. Additionally, the study may guide therapeutic interventions aiming to optimize hemodynamics and enhance Fontan longevity for individual patients.

Clinical features and drug-resistance in pediatric epilepsy with co-occurring autism: A retrospective comparative cohort study.

OBJECTIVE: We conducted a retrospective comparative cohort study to determine the phenotypic and real-world management differences in children with epilepsy and co-occurring autism as compared to those without autism. METHODS: Clinical variables, EEG, brain MRI, genetic results, medical and non-medical treatment were compared between 156 children with both epilepsy and autism, 156 randomly selected and 156 demographically matched children with epilepsy only. Logistic regression analyses were conducted to determine predictors of drug-resistant epilepsy (DRE). RESULTS: As compared to the'matched' cohort, more patients with autism had generalized motor seizures although not statistically significant after Benjamini-Hochberg correction (54.5%, vs 42.3%, p = .0314); they had a lower rate of electroclinical syndromes (12.8%, vs 30.1%, p = .0002). There were more incidental MRI findings but less positive MRI findings to explain their epilepsy in children with autism (26.3%, vs 13.8% and 14.3%, vs 34.2%, respectively; p = .0003). In addition, LEV, LTG, and VPA were the most common ASMs prescribed to children with autism, as opposed to LEV, OXC, and LTG in children without autism. No difference in the major EEG abnormalities was observed. Although the rates of DRE were similar (24.8%, vs 26.6%, p = .7203), we identified two clinical and five electrographic correlates with DRE in children with both epilepsy and autism and a final prediction modeling of DRE that included EEG ictal findings, focal onset seizures, generalized motor seizures, abnormal EEG background, age of epilepsy onset, and history of SE, which were distinct from those in children without autism. SIGNIFICANCE: Our study indicates that detailed seizure history and EEG findings are the most important evaluation and prediction tools for the development of DRE in children with epilepsy and co-occurring autism. Further studies of epilepsy in specific autism subgroups based on their etiology and clinical severity are warranted.

Health-related Internet Use by Caregivers of Children and Adolescents With Cancer.

Caregivers of children with cancer have needs for information and social support related to their child's diagnosis. The internet serves as a resource to help meet these needs. There is growing interest in health-related internet use (HRIU) by caregivers of pediatric patients as the internet rapidly evolves. This survey study describes patterns of internet use by caregivers of children with cancer and examines associations between socioeconomic status and internet use. 114 caregivers participated between 2014 and 2016. The majority (82%) reported frequent general internet use, but fewer (25-54%) reported frequent HRIU. Very few respondents (4%) reported difficulty accessing the internet; those reporting difficulty were more likely to report lower income, public/no insurance, and lower educational attainment. There were no consistent associations between socioeconomic status variables and frequency of HRIU. Less than half (43%) of caregivers reported that their internet use raised questions that they discussed or planned to discuss with the child's nurse or doctor, and only 4% reported having changed medical decisions based on information found on the internet. We conclude that caregivers of children with cancer engage in HRIU, and this is an area for improvement in oncology anticipatory guidance and family-centered care.

Preventing the Early Introduction of Juice and Sugar-Sweetened Beverages in Infants' Diets: A Randomized Controlled Trial.

A randomized controlled trial was conducted to determine whether a simple educational intervention targeting parents of young infants could have an impact on the consumption of juice and sugar-sweetened beverages (SSBs) in early childhood and decrease overweight and obesity rates. Parents of 2- to 4-month-old infants were randomized into intervention (n = 67) and control (n = 77) groups. Parents completed questionnaires about juice and SSB consumption and knowledge at baseline and 1-year follow-up. Intervention parents received informational handouts and watched videos about the health effects of juice and SSBs. Knowledge about juice increased significantly in the intervention group compared with control (P < .01) and was significantly higher in black/African American parents (P < .05) and those with some college education (P < .05). The intervention had a significant impact on the knowledge gained by parents about the health effects of juice and SSBs but did not decrease the consumption of sugary drinks or change children's weight status.

Constructing, validating, and updating machine learning models to predict survival in children with Ebola Virus Disease.

BACKGROUND: Ebola Virus Disease (EVD) causes high case fatality rates (CFRs) in young children, yet there are limited data focusing on predicting mortality in pediatric patients. Here we present machine learning-derived prognostic models to predict clinical outcomes in children infected with Ebola virus. METHODS: Using retrospective data from the Ebola Data Platform, we investigated children with EVD from the West African EVD outbreak in 2014-2016. Elastic net regularization was used to create a prognostic model for EVD mortality. In addition to external validation with data from the 2018-2020 EVD epidemic in the Democratic Republic of the Congo (DRC), we updated the model using selected serum biomarkers. FINDINGS: Pediatric EVD mortality was significantly associated with younger age, lower PCR cycle threshold (Ct) values, unexplained bleeding, respiratory distress, bone/muscle pain, anorexia, dysphagia, and diarrhea. These variables were combined to develop the newly described EVD Prognosis in Children (EPiC) predictive model. The area under the receiver operating characteristic curve (AUC) for EPiC was 0.77 (95% CI: 0.74-0.81) in the West Africa derivation dataset and 0.76 (95% CI: 0.64-0.88) in the DRC validation dataset. Updating the model with peak aspartate aminotransferase (AST) or creatinine kinase (CK) measured within the first 48 hours after admission increased the AUC to 0.90 (0.77-1.00) and 0.87 (0.74-1.00), respectively. CONCLUSION: The novel EPiC prognostic model that incorporates clinical information and commonly used biochemical tests, such as AST and CK, can be used to predict mortality in children with EVD.

Risk Prediction Score for Pediatric Patients with Suspected Ebola Virus Disease.

Rapid diagnostic tools for children with Ebola virus disease (EVD) are needed to expedite isolation and treatment. To evaluate a predictive diagnostic tool, we examined retrospective data (2014-2015) from the International Medical Corps Ebola Treatment Centers in West Africa. We incorporated statistically derived candidate predictors into a 7-point Pediatric Ebola Risk Score. Evidence of bleeding or having known or no known Ebola contacts was positively associated with an EVD diagnosis, whereas abdominal pain was negatively associated. Model discrimination using area under the curve (AUC) was 0.87, which outperforms the World Health Organization criteria (AUC 0.56). External validation, performed by using data from International Medical Corps Ebola Treatment Centers in the Democratic Republic of the Congo during 2018-2019, showed an AUC of 0.70. External validation showed that discrimination achieved by using World Health Organization criteria was similar; however, the Pediatric Ebola Risk Score is simpler to use.

Delays in Presentation of New Onset Diabetes at the Start of the COVID-19 Pandemic.

OBJECTIVE: To compare the frequency, severity of presentation and initial presentations of new onset diabetes mellitus (DM) in youth in Rhode Island during the early phase of the COVID-19 pandemic compared to the same time frame in 2018 and 2019. METHODS: A retrospective cohort study of youth treated for new onset DM at Hasbro Children's Hospital between March 1 and May 15, 2020, compared to those diagnosed in the same period in 2018 and 2019. RESULTS: Fewer youth were diagnosed with new onset DM in Spring 2020 and the percentage of youth with DKA at time of DM diagnosis was higher in Spring 2020 compared to prior years (p=0.048). Age, gender, and DKA complications did not differ by year. CONCLUSION: Nearly 50% fewer youth were diagnosed with DM at the start of the COVID-19 pandemic compared to years prior, and those diagnosed with new onset DM in Spring 2020 were more likely to present with DKA. Delays in both initial health care evaluation and the recognition of DM symptoms may have contributed to the decline in overall DM diagnoses and the more severe presentations. Identification of DM symptoms is essential, especially during future surges of COVID-19 or other events that impact the healthcare system, to reduce the risk of DM complications including DKA.

Multidisciplinary Health Care Professionals' Perceptions About Pediatric End of Life Discussions: A Cross-Sectional Survey and Needs Analysis.

BACKGROUND: Pediatric end of life (EOL) care involves complex coordination of providers from multiple disciplines. Many of these providers' experiences have not been completely described. AIM: This study aims to explicate the alignment and divergence of health care professionals' perceptions of the training, timelines, comfort, and effectiveness of pediatric EOL discussions as well as identify methods to improve medical education training. DESIGN: A cross-sectional survey was conducted. Analyses included Fisher's exact and post-hoc tests for all pairwise comparisons. SETTING/PARTICIPANTS: A total of 160 of 508 eligible participants at a single academic Department of Pediatrics completed the survey (response rate 31%). Participants included attending physicians, fellows, residents, mid-level providers, nurses, and social workers. RESULTS: Sixty percent thought EOL discussions occurred late and 70% thought discussions should occur earlier. Attending physicians were more likely to think discussions occurred late and should occur earlier (P <.01). Residents and fellows were more likely to think participating in and leading discussions was stressful (P <.02 and P <.01, respectively). Respondents that were female, younger than forty years old, had been in their provider role less than five years, or were residents and fellows were more likely to agree that these discussions led to changes in plan of patient care (P <.05). CONCLUSIONS: The majority of multidisciplinary pediatric health care professionals believe pediatric EOL discussions are stressful, occur too late, and should occur earlier. Future efforts in medical education should prioritize curriculum development focusing on workshops and simulations.

Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown. Objective: To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life. Design, Setting, and Participants: A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used by symptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020. Interventions: n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period. Main Outcomes and Measures: AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing. Results: Of 446 participants who initiated (mean [SD] age, 58 [14] years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P < .001). In a meta-analysis of the individualized trials, only exposure to alcohol was associated with significantly heightened risks of AF events. Conclusions and Relevance: n-of-1 Testing of AF triggers did not improve AF-associated quality of life but was associated with a reduction in AF events. Acute exposure to alcohol increased AF risk, with no evidence that other exposures, including caffeine, more commonly triggered AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03323099.

Clinical, Sociodemographic and Environmental Risk Factors for Acute Bacterial Diarrhea among Adults and Children over Five Years in Bangladesh.

In 2016, diarrheal disease was the eighth leading cause of mortality globally accounting for over 1.6 million deaths with the majority of deaths in adults and children over 5 years. This study aims to investigate the clinical, sociodemographic, and environmental risk factors associated with common bacterial acute diarrhea among adults and children over 5. Data were collected from March 2019 to March 2020 in patients over 5 years presenting with acute gastroenteritis at icddr,b. Stool samples were collected from each patient for culture and polymerase chain reaction (PCR) testing. Bivariate associations between independent variables and stool-testing indicating bacterial etiology were calculated. This analysis included 2,133 diarrheal patients of whom a bacterial enteropathogen was identified in 1,537 (72%). Detection of bacteria was associated with: younger age (OR 0.92; 95% CI: 0.88-0.96), lower mean arterial pressure (OR 0.84; 95% CI: 0.79-0.89), heart rate (OR 1.06; 95% CI: 1.01-1.10), percentage dehydration (OR 1.33; 95% CI: 1.13-1.55), respiration rate (OR 1.23; 95% CI: 1.04-1.46), lower mid-upper arm circumference (OR 0.97; 95% CI: 0.94-0.99), confused/lethargic mental status (OR 1.85; 95% CI: 1.11-3.25), rice watery stool (OR 1.92; 95% CI: 1.54-2.41), and vomiting more than three times in the past 24 hours (OR 1.30; 95% CI: 1.06-1.58). Higher monthly income (OR 0.92; 95% CI: 0.86-0.98), > 8 years of education (OR 0.79; 95% CI: 0.63-1.00), and having more than five people living at home (OR 0.80; 95% CI: 0.66-0.98) were associated with lower odds of bacterial diarrhea. These findings may help guide the development of predictive tools to aid in identifying patients with bacterial diarrhea for timely and appropriate use of antibiotics.

Changes in Sick Visits at an Academic Pediatric Primary Care Practice due to the COVID-19 Pandemic.

BACKGROUND/OBJECTIVE: The COVID-19 pandemic decreased pediatric patient volumes; however, details regarding patterns of use within primary care sick visits are not well understood. METHODS: We performed a retrospective chart review of sick visits in an academic primary care clinic from March-August 2019 and 2020 and recorded demographics and visit diagnoses. Descriptive statistics, Chi-square, and Fisher's exact tests were used to compare the two time periods. RESULTS: Patient age, gender, and insurance type were similar across years. In 2020, there were 1,868 sick visits (247 telehealth, 4%-36% of monthly visits) compared to 4,007 (0 telehealth) in 2019. The proportion of infectious diagnoses decreased (35% vs 48%); non-infectious diagnoses increased, including dermatological (25% vs 19%) and genitourinary/reproductive (9% vs. 6%) diagnoses.  Conclusion: Similar to pediatric emergency departments, we found decreased primary care sick visits. Telehealth increased in 2020 and varied with COVID-19 community prevalence. Visits for contagious illnesses decreased in 2020, likely related to mitigation measures.

Visits for Possible COVID-19 in a Pediatric Primary Care Practice Early in the Pandemic.

BACKGROUND: Children with COVID-19 usually present with mild symptoms. We characterize visits with respect to symptoms and testing in the outpatient setting. METHODS: A retrospective chart review of sick visits in a pediatric academic primary care clinic April-August 2020. We included possible COVID-19 cases, or "persons under investigation" (PUIs), recording symptoms, positive contacts, and COVID-19 testing. Descriptive statistics and Chi-square or Fisher's exact tests for comparisons were used. RESULTS: 32% (476/1,474) of sick visits were PUIs; 20% were telehealth. Symptoms most commonly reported were fever, congestion/rhinorrhea and cough. 76% of PUIs were tested for COVID-19. Only presence of COVID-19 contacts and loss of taste/smell were significantly associated with positive tests (p<0.001). CONCLUSION: Nearly a third of sick visits in an academic pediatric practice were seen for possible COVID-19 symptoms and most were tested. The majority with and without COVID-19 had fever, congestion and/or cough. Our findings suggest low thresholds for testing in children.

Multidrug-resistant enteric pathogens in older children and adults with diarrhea in Bangladesh: epidemiology and risk factors.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study's aim was to characterize the prevalence of MDR enteric pathogens isolated from patients with acute diarrhea in Dhaka, Bangladesh, and assess a wide range of risk factors associated with MDR. METHODS: This study was a secondary analysis of data collected from children over 5 years, adults, and elderly patients with acute diarrhea at the International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka Hospital between March 2019 and March 2020. Clinical, historical, socio-environmental information, and a stool sample for culture and antimicrobial susceptibility testing were collected from each patient. Univariate statistics and multiple logistic regression were used to assess the prevalence of MDR among enteric pathogens and the association between independent variables and presence of MRDOs among culture-positive patients. RESULTS: A total of 1198 patients had pathogens isolated by stool culture with antimicrobial susceptibility results. Among culture-positive patients, the prevalence of MDR was 54.3%. The prevalence of MDR was highest in Aeromonas spp. (81.5%), followed by Campylobacter spp. (72.1%), Vibrio cholerae (28.1%), Shigella spp. (26.2%), and Salmonella spp. (5.2%). Factors associated with having MDRO in multiple logistic regression included longer transport time to hospital (>90 min), greater stool frequency, prior antibiotic use prior to hospital presentation, and non-flush toilet use. However, pseudo-R2 was low 0.086, indicating that other unmeasured variables need to be considered to build a more robust predictive model of MDR. CONCLUSIONS: MDR enteric pathogens were common in this study population with clinical, historical, and socio-environmental risk factors associated with MDROs. These findings may help guide clinical decision-making regarding antibiotic use and selection in patients at greatest risk of complications due to MDROs. Further prospective research is urgently needed to determine what additional factors place patients at greatest risk of MDRO, and the best strategies to mitigate the spread of MDR in enteric pathogens.

Clinical and socio-environmental determinants of multidrug-resistant vibrio cholerae 01 in older children and adults in Bangladesh.

OBJECTIVES: Few studies have evaluated determinants of multidrug-resistant (MDR) Vibrio cholerae O1 in older children and adults. This study aimed to characterize the prevalence of MDR V. cholerae O1 and associated risk factors among patients over five years of age in Bangladesh. METHODS: Stool culture and antimicrobial susceptibility testing were performed as a part of a larger study at Dhaka Hospital in Bangladesh from March 2019-March 2020. Univariate statistics and multiple logistic regression were used to assess the association between a range of variables and MDR V. cholerae O1. RESULTS: MDR was found in 175 of 623 (28.1%) V. cholerae O1 isolates. High levels of resistance were found to erythromycin (99.2%), trimethoprim-sulfamethoxazole (99.7%), and ampicillin (88.9%), while susceptibility was high to tetracyclines (99.7%), azithromycin (99.2%), ciprofloxacin (99.8%), and cephalosporins (98.6%). MDR was associated with prior antibiotic use, longer transport time to hospital, higher income, non-flush toilet use, greater stool frequency, lower blood pressure, lower mid-upper arm circumference, and lower percent dehydration. CONCLUSIONS: MDR V. cholerae O1 was common among patients over five in an urban hospital in Bangladesh. Significant factors associated with MDR may be actionable in identifying patients with a high likelihood of MDR.

Ledipasvir/Sofosbuvir Effectively Treats Hepatitis C Virus Infections in an Underserved Population.

BACKGROUND: Underserved populations have an unequal burden of HCV infections and poor outcomes with interferon-based treatments. Direct-acting antivirals have the potential to reduce these inequalities. AIMS: We aimed to estimate sustained virologic response (SVR) following treatment with sofosbuvir-based regimens for HCV infections among underserved individuals and summarize the frequency of SVR across published studies of underserved populations. METHODS: We used data from a clinical cohort of patients aged ≥ 18 years who initiated sofosbuvir-based regimens for HCV infection between February 2014 and June 2016 at an urban public hospital network that serves as the healthcare safety-net for Tarrant County, Texas. We estimated SVR with corresponding 95% confidence limits (CL). In addition, we systematically reviewed the evidence to identify other studies of direct-acting antivirals among underserved populations. RESULTS: Our study population comprised 435 patients. The majority of patients were aged ≥ 50 years (76%), male (52%), non-Hispanic White (54%), HCV genotype 1 (79%) and treated with ledipasvir/sofosbuvir (69%). Overall SVR was 89% (95% CL 86, 92%) and highest for ledipasvir/sofosbuvir (SVR = 95%, 95% CL 92, 97%). The reported SVR following direct-acting antivirals among 837 underserved patients from three other studies ranged between 90 and 99%. CONCLUSIONS: Our results suggest that direct-acting antivirals, particularly ledipasvir/sofosbuvir, are generally effective for achieving SVR among underserved patients with HCV infections and may help reduce inequalities in HCV prevalence and outcomes for this vulnerable population.

Comparative effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens for HCV infection.

BACKGROUND: Real-world studies have aimed to compare the effects of 8- and 12-week ledipasvir/sofosbuvir regimens on sustained virological response (SVR) among HCV infection genotype-1 (HCV-1) treatment-naive patients. Nevertheless, real-world comparative effectiveness studies pose unique challenges, such as confounding by indication, that were not adequately addressed in prior studies. We thus aimed to address limitations in prior studies and compare overall- and subgroup-specific effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens among HCV-1 treatment-naive patients. METHODS: Patients eligible for our study were aged ≥18 years and initiated 8- or 12-week ledipasvir/sofosbuvir regimens for treatment-naive HCV-1 at an urban public hospital network. We excluded patients with HIV or cirrhosis. We used marginal structural models to estimate overall and subgroup-specific risk ratios (RRs) and 95% confidence limits (CL) comparing the effect of 8- and 12-week ledipasvir/sofosbuvir regimens on 12-week SVR. RESULTS: Our study population comprised 191 patients. Among both regimens, the majority were aged >50 years, non-Hispanic White and uninsured. The overall risk of SVR was comparable between the 8- and 12-week regimens (RR=1.01, 95% CL: 0.92, 1.11). The risk of SVR did not vary by race/ethnicity (non-Hispanic Black: RR=1.01, 95% CL: 0.84, 1.21; non-Hispanic White: RR=1.01, 95% CL: 0.89, 1.04). CONCLUSIONS: Our real-world results suggest that 8- and 12-week ledipasvir/sofosbuvir have comparable effects on SVR among HCV-1 patients without cirrhosis or HIV. In addition, the comparable effectiveness of 8- and 12-week regimens among non-Hispanic Black individuals adds to the growing body of evidence that supports the removal of race-based treatment guidelines.